Abstract
1704 Identifying clusters of longitudinal autoantibody profiles associated with systemic lupus erythematosus disease outcomes
Lupus science & medicine, v 8(Suppl 2), pp A70-A72
04 Nov 2021
Abstract
BackgroundPrior studies of SLE clusters based on autoantibodies have utilized cross-sectional data from single centers. We applied clustering techniques to longitudinal and comprehensive autoantibody data from a large multinational, multi-ethnic inception cohort of well characterized SLE patients to identify clusters associated with disease outcomes.MethodsWe used demographic, clinical, and serological data at enrolment and follow-up visits years 3 and 5 from 805 patients who fulfilled the 1997 Updated ACR SLE criteria and were enrolled within 15 months of diagnosis. For each visit, ANA, dsDNA, Sm, U1-RNP, SSA/Ro60, SSB/La, Ro52/TRIM21, histones, ribosomal P, Jo-1, centromere B, PCNA, anti-DFS70, lupus anticoagulant (LAC), IgG and IgM for anticardiolipin, anti–β2GP1, and aPS/PT, and IgG anti-β2GP1 D1 were performed at a single lab (except LAC). K-means clustering algorithm on principal component analysis (10 dimensions) transformed longitudinal ANA/autoantibody profiles was used. We compared cluster demographic/clinical outcomes, including longitudinal disease activity (total and adjusted mean SLEDAI-2K), SLICC/ACR damage index and organ-specific domains, SLE therapies, and survival, using one-way ANOVA test and a Benjamini-Hochberg correction with false discovery rate alpha=0.05. Results were visualized using t-distributed stochastic neighbor embedding.ResultsFour unique patient clusters were identified (table 1). Cluster 1, characterized by high frequency of anti-Sm and anti-RNP over time, was the youngest group at disease onset with a high proportion of subjects of Asian and African ancestry. At year 5, they had the highest disease activity, were more likely to have active hematologic and mucocutaneous involvement, and to be on/exposed to immunosuppressants/biologics. Cluster 2, the largest cluster, had low frequency of anti-dsDNA, were oldest at disease onset, and at year 5, had the lowest disease activity, and were least likely to have nephritis and be on/exposed to immunosuppressants/biologics. Cluster 3 had the highest frequency of antiphospholipid antibodies over time, were more likely to be of European ancestry, have an elevated BMI, be former smokers, and by year 5, to have nephritis, neuropsychiatric involvement, including strokes and seizures (SLICC/ACR damage index). Cluster 4 was characterized by anti-SSA/Ro60, SSB/La, Ro52/TRIM21, histone antibodies, and low complements at year 5. Overall, survival of the 805 subjects was 94% at 5 years, and none of the clusters predicted survival.Abstract 1704 Table 1Demographic and clinical characteristics that were statistically significant1 at baseline and five-year follow-up between the four SLE longitudinal autoantibody clusters Group 1 (n=137) Group 2 (n=377) Group 3 (n=79) Group 4 (n=212) p-value FDR Enrolment Demographics Mean Age of Diagnosis (SD), yrs 32.0 (10.8) 36.9 (13.9) 32.9 (14.0) 34.9 (14.0) 0.003 0.003 % Ethnicity White 32 62 68 43 <0.001 <0.001 Asian 31 20 14 31 0.001 0.004 African 27 10 6 15 <0.001 <0.001 Mean BMI (SD), kg/m2 25.5 (6.1) 26.4 (6.6) 26.9 (6.9) 24.9 (5.4) 0.015 0.041 % Former smoker 17 23 28 12 0.002 0.005 Clinical Characteristics at Year 5 Follow-Up % Nephritis2 42 30 46 42 0.028 0.009 Mean SLEDAI-2K Score (SD) Total Score3 4.3 (4.5) 2.3 (3.3) 3.0 (3.1) 3.6 (3.2) <0.001 <0.001 Adjusted Mean Score4 4.3 (3.1) 2.9 (2.5) 3.7 (2.2) 4.1 (2.6) <0.001 <0.001 Hematological Subscale 0.16 (0.39) 0.06 (0.23) 0.06 (0.25) 0.11 (0.31) 0.003 0.008 Immunological Subscale 1.7 (1.69) 0.82 (1.30) 1.82 (1.54) 2.12 (1.62) <0.001 <0.001 Low Complement 0.82 (0.99) 0.43 (0.82) 1.01 (1.01) 1.03 (1.00) <0.001 <0.001 Mucocutaneous Subscale 0.83 (1.98) 0.33 (0.87) 0.20 (0.69) 0.37 (0.97) <0.001 <0.001 Mean SLICC Damage Index (SD) Neuropsychiatric Domain 0.11 (0.40) 0.16 (0.52) 0.32 (0.82) 0.08 (0.32) 0.003 0.009 Cerebrovascular accident 0.02 (0.15) 0.04 (0.22) 0.14 (0.45) 0.04 (0.19) 0.002 0.007 Seizures 0.01 (0.12) 0.03 (0.16) 0.08 (0.27) <0.01(0.07) 0.004 0.012 Skin Domain 0.15 (0.42) 0.07 (0.29) 0.03 (0.16) 0.07 (0.28) 0.011 0.030 Alopecia 0.11 (0.31) 0.04 (0.20) 0.01 (0.11) 0.04 (0.19) 0.002 0.007 Medications Ever % Immunosuppressives/Biologics 79 60 61 72 <0.001 <0.001 % Imuran 51 31 41 41 <0.001 <0.001 % Mycophenolic Acid 34 21 18 25 0.014 0.039 Medications Current % Immunosuppressives/Biologics 62 45 48 55 0.004 0.012 1. Comparison between cluster groups using one-way ANOVA test and a Benjamini-Hochberg correction with false discovery rate (FDR) alpha = 0.052. Lupus nephritis was diagnosed by renal biopsy or fulfillment of the renal item on the ACR classification criteria.3. The total score of SLEDAI-2K is the sum of all 24 descriptor scores. The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity.4. A measurement of lupus disease activity over time determined by the calculation of the area under the curve of SLEDAI-2K over time by adding the area of each of the blocks of visit interval and then dividing by the length of time for the whole period.Abbreviations: BMI, body mass index; SD, standard deviation; SLEDAI-2K, Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC, Systemic Lupus International Collaborating Clinics; yrs, years. ConclusionsFour SLE patient clusters associated with disease activity, organ involvement, and treatment were identified in this analysis of longitudinal ANA/autoantibody profiles in relation to SLE outcomes, suggesting these subsets might be identifiable based on extended autoantibody profiles early in disease and carry prognostic information.AcknowledgmentsThis study is presented on behalf of SLICC. We would also like to acknowledge the technical assistance of Ms. Haiyan Hou (MitogenDx Laboratory).
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- Title
- 1704 Identifying clusters of longitudinal autoantibody profiles associated with systemic lupus erythematosus disease outcomes
- Creators
- May Y Choi - University of CalgaryIrene Chen - Massachusetts Institute of TechnologyAnn Clarke - University of CalgaryMarvin J Fritzler - University of CalgaryKatherine A Buhler - University of CalgaryMurray Urowitz - Toronto Western HospitalJohn G Hanly - Queen Elizabeth II Health Sciences CentreCaroline Gordon - University of BirminghamYvan St Pierre - McGill University Health CentreSang-Cheol Bae - Hanyang University Seoul HospitalJuanita Romero Diaz - Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránJorge Sanchez-Guerrero - Mount Sinai HospitalSasha Bernatsky - McGill University Health CentreDaniel Wallace - Cedars-Sinai Medical CenterDavid Isenberg - University College LondonAnisur Rahman - University College LondonJoan T Merrill - Oklahoma Medical Research FoundationPaul R Fortin - Université LavalDafna D Gladman - Toronto Western HospitalIan Bruce - University of ManchesterMichelle A Petri - Johns Hopkins MedicineEllen Ginzler - SUNY Downstate Health Sciences UniversityMary Anne Dooley - University of North Carolina at Chapel HillRosalind Ramsey-Goldman - Northwestern UniversitySusan Manzi - Allegheny Health NetworkAndreas Jonsen - Lund UniversityGraciela S Alarcon - University of Alabama at BirminghamRonald FVan Vollenhoven - University of AmsterdamCynthia Aranow - Feinstein Institute for Medical ResearchMeggan Mackay - Feinstein Institute for Medical ResearchGuillermo Ruiz-Irastorza - University of the Basque CountrySam Lim - Emory UniversityMurat Inanc - Istanbul UniversityKenneth C Kalunian - University of California, San DiegoSoren Jacobsen - Copenhagen University HospitalChristine Peschken - University of ManitobaDiane Kamen - Medical University of South CarolinaAnca Askanase - New York University Langone Orthopedic HospitalDavid Sontag - Massachusetts Institute of TechnologyJill Buyon - New York UniversityKaren H Costenbader - Brigham and Women's Hospital
- Publication Details
- Lupus science & medicine, v 8(Suppl 2), pp A70-A72
- Publisher
- Lupus Foundation of America
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- General Internal Medicine
- Other Identifier
- 991021934001504721